Tug of War at Air-Water Interface: Understanding Lipid-Nanoparticle and Lipid-Protein Interaction Associated With Lung Surfactants at a Molecular Level

Lung surfactants [LS] are a complex mixture of lipids and proteins that line the air-water interface in the alveoli of the lungs. They lower the work of breathing by reducing the surface tension and also form a line of defense against particles small enough to enter the respiratory tract. A deficiency of LS may lead to the fatal Neonatal Respiratory Distress Syndrome [NRDS] in premature infants, whereas, an impairment may cause Acute Respiratory Distress Syndrome [ARDS], irrespective of the age. Medical intervention in the form of Surfactant Replacement Therapy [SRT] becomes a lifesaver in such cases. Developing synthetic LS with efficacy in treating ARDS has therefore been a focus of this work. Further, with the rapid development in commercial and biomedical applications of engineered nanoparticles (ENPs), concerns regarding the effect of inhaled nanoparticles on LS function also need to be addressed. In this work, we have used a carbon-based ENP to understand their interactions with model LS. Our studies revealed that the alkyl chain saturation and head group charge of the phospholipids that form the major components of the LS play modulate phospholipid-nanoparticle interactions. We monitored the effect of Engineered Carbon Nanodiamonds [ECN] on five lipid compositions. In a zwitterionic environment, the nanoparticle was line active and favored the phospholipid domain boundaries. However, in an anionic environment, the nanoparticles reduced the packing density between domains. The electrostatic charge interaction was found to be more dominant. We also observed the tug of war between a synthetic surfactant protein (analog of natural surfactant protein, SPB) called MiniB and cholesterol. MiniB increased the line tension of the domains whereas cholesterol reduced the same. MiniB also helped in forming reversible collapse at low surface tension, which in turn saved material loss to the bulk. A lower concentration of both proved to be effective in increasing the surface activity of LS

Interaction of Biomolecules at the Air-Water Interface: Evaluating the Role of Lipid Composition when Interacting with Lung Surfactant Proteins and Engineered Carbon Nanodiamonds

Lung surfactants (LSs) are a complex mixture of lipids and proteins that are found in the alveolar lining of the lungs. Their primary objective lies in lowering the surface tension of the aqueous layer on which they reside. By doing so, LSs reduce the energy involved in breathing, and any loss/ dysfunction of the surfactants can cause fatal respiratory complications. Successful treatment methods require a thorough understanding of the biophysical properties of the LSs, and their interaction with any material that may come in contact. This dissertation aims at evaluating the interaction of the different lipids found in the surfactant pool with such plausible candidates at the air-water interface. Engineered carbon nanodiamonds (ECNs) is selected because of their potential in becoming a candidate for drug delivery through the respiratory tract. Therefore, it is necessary to evaluate any possible toxic outcome from ECNs. Here, we observe that both the lipid headgroup charge and the tail saturation impact the biophysical properties of the monolayer. We also evaluate the impact of the protein, Mini-B, which is a synthetic analog of the native surfactant protein, SP-B, on the biophysical properties of the LSs. Mini-B is a suitable candidate for surfactant replacement therapy (SRT), which is associated with lung diseases. Thus, Mini-B needs a thorough biophysical analysis. Lastly, we observe the effectiveness of Mini-B in countering the deleterious effects of cholesterol. Cholesterol is found in the native mixture and helps in fluidizing the monolayer. However, cholesterol has been reported to have some harmful impact on the LSs. Thus, it is a highly disputed component in SRT, with some formulations removing cholesterol from their product. We observe that 1 to 5 wt.% of Mini-B can counter the harmful effects of small quantities of cholesterol, providing a wholesome mixture

Tug of War in Lung Surfactant Components: MiniB Dominates over Cholesterol during Lipid Domain Formation

This is the published version. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.Lung surfactants (LS), a complex mixture of lipids and proteins present in the alveolar lining of lungs, help in lowering surface tension to near zero at expiration. Deficiency of this surfactant can lead to Neonatal Respiratory Distress Syndrome in infants, while a dysfunction of LS can cause Acute Respiratory Distress Syndrome (ARDS) that affects patients irrespective of age. Successful medical intervention such as surfactant replacement therapy (SRT) requires a good understanding of surfactant composition and function. Currently there is no consensus on the composition of LS used in SRT, particularly the interactions between components making up this mixture. Our objective was to understand the interaction of cholesterol (a component whose role and even presence in SRT is highly debated) and MiniB (a synthetic protein mimic of native surfactant protein SP-B) at air-water interface. We report the alteration in lipid domain formation of films containing 1,2-dipalmitoyl- sn- glycero- 3- phosphocholine (DPPC): 1- palmitoyl- 2- oleoyl- sn- glycero- 3- phosphatidylglycerol (POPG) in the ratio 7:3 under the influence of varying concentrations of MiniB and cholesterol. Fluorescence imaging under constant compression, along with analysis of domain size distributions, reveals that MiniB increases line tension between lipid domains, and prefers to stay in fluid POPG regions, making the liquid-ordered domains smaller in size. Small amounts of cholesterol prefer packed domains, stretching them into spirals during the process, lowering their line tension. In both cases, higher concentration yields more prominent consequences in terms of the stated changes. However, mixture containing both cholesterol and MiniB shows reduction in domain size with no changes in domain shape. This suggests the dominance of MiniB over cholesterol when interacting with lipid domains, which may have important effects on the performance of synthetic LS

Impact of Engineered Carbon Nanodiamonds on the Collapse Mechanism of Model Lung Surfactant Monolayers at the Air-Water Interface

This work is licensed under a Creative Commons Attribution 4.0 International License.Understanding interactions between inhaled nanoparticles and lung surfactants (LS) present at the air-water interface in the lung, is critical to assessing the toxicity of these nanoparticles. Specifically, in this work, we assess the impact of engineered carbon nanoparticles (ECN) on the ability of healthy LS to undergo reversible collapse, which is essential for proper functioning of LS. Using a Langmuir trough, multiple compression-expansion cycles are performed to assess changes in the surface pressure vs. area isotherms with time and continuous cyclic compression-expansion. Further, theoretical analysis of the isotherms is used to calculate the ability of these lipid systems to retain material during monolayer collapse, due to interactions with ECNs. These results are complemented with fluorescence images of alterations in collapse mechanisms in these monolayer films. Four different model phospholipid systems, that mimic the major compositions of LS, are used in this study. Together, our results show that the ECN does not impact the mechanism of collapse. However, the ability to retain material at the interface during monolayer collapse, as well as re-incorporation of material after a compression-expansion cycle is altered to varying extent by ECNs and depends on the composition of the lipid mixtures

Contact‐Free Remote Manipulation of Hydrogel Properties Using Light‐Triggerable Nanoparticles: A Materials Science Perspective for Biomedical Applications

Considerable progress has been made in synthesizing “intelligent”, biodegradable hydrogels that undergo rapid changes in physicochemical properties once exposed to external stimuli. These advantageous properties of stimulus-triggered materials make them highly appealing to diverse biomedical applications. Of late, research on the incorporation of light-triggered nanoparticles (NPs) into polymeric hydrogel networks has gained momentum due to their ability to remotely tune hydrogel properties using facile, contact-free approaches, such as adjustment of wavelength and intensity of light source. These multi-functional NPs, in combination with tissue-mimicking hydrogels, are increasingly being used for on-demand drug release, preparing diagnostic kits, and fabricating smart scaffolds. Here, the authors discuss the atomic behavior of different NPs in the presence of light, and critically review the mechanisms by which NPs convert light stimuli into heat energy. Then, they explain how these NPs impact the mechanical properties and rheological behavior of NPs-impregnated hydrogels. Understanding the rheological behavior of nanocomposite hydrogels using different sophisticated strategies, including computer-assisted machine learning, is critical for designing the next generation of drug delivery systems. Next, they highlight the salient strategies that have been used to apply light-induced nanocomposites for diverse biomedical applications and provide an outlook for the further improvement of these NPs-driven light-responsive hydrogels

Harnessing the physicochemical properties of DNA as a multifunctional biomaterial for biomedical and other applications

The biological purpose of DNA is to store, replicate, and convey genetic information in cells. Progress in molecular genetics have led to its widespread applications in gene editing, gene therapy, and forensic science. However, in addition to its role as a genetic material, DNA has also emerged as a nongenetic, generic material for diverse biomedical applications. DNA is essentially a natural biopolymer that can be precisely programed by simple chemical modifications to construct materials with desired mechanical, biological, and structural properties. This review critically deciphers the chemical tools and strategies that are currently being employed to harness the nongenetic functions of DNA. Here, the primary product of interest has been crosslinked, hydrated polymers, or hydrogels. State-of-the-art applications of macroscopic, DNA-based hydrogels in the fields of environment, electrochemistry, biologics delivery, and regenerative therapy have been extensively reviewed. Additionally, the review encompasses the status of DNA as a clinically and commercially viable material and provides insight into future possibilities

Leveraging the advancements in functional biomaterials and scaffold fabrication technologies for chronic wound healing applications

Exploring new avenues for clinical management of chronic wounds holds the key to eliminating socioeconomic burdens and health-related concerns associated with this silent killer. Engineered biomaterials offer great promise for repair and regeneration of chronic wounds because of their ability to deliver therapeutics, protect the wound environment, and support the skin matrices to facilitate tissue growth. This mini review presents recent advances in biomaterial functionalities for enhancing wound healing and demonstrates a move from sub-optimal methods to multi-functionalized treatment approaches. In this context, we discuss the recently reported biomaterial characteristics such as bioadhesiveness, antimicrobial properties, proangiogenic attributes, and anti-inflammatory properties that promote chronic wound healing. In addition, we highlight the necessary mechanical and mass transport properties of such biomaterials. Then, we discuss the characteristic properties of various biomaterial templates, including hydrogels, cryogels, nanomaterials, and biomolecule-functionalized materials. These biomaterials can be microfabricated into various structures, including smart patches, microneedles, electrospun scaffolds, and 3D-bioprinted structures, to advance the field of biomaterial scaffolds for effective wound healing. Finally, we provide an outlook on the future while emphasizing the need for their detailed functional behaviour and inflammatory response studies in a complex in vivo environment for superior clinical outcomes and reduced regulatory hurdles

Engineering multifunctional adhesive hydrogel patches for biomedical applications

Traditional patches, such as sticking plaster or acrylic adhesives used for over a hundred years, lack functionality. To address this issue of poor functionality, adhesive hydrogel patches have emerged as an efficient bioactive multifunctional alternative. Hydrogels are three-dimensional, water-swellable, and polymeric materials closely resembling the native tissue architecture. The physicochemical properties of hydrogels can be modified easily, allowing them to be suitable for various biomedical applications. Moreover, adhesive properties can be imparted to hydrogels through physicochemical manipulations, making them ideal candidates for supplementing or replacing traditional sticking plaster. As a result, sticky hydrogel patches are widely used for transdermal drug delivery and have even found commercial purposes. Beyond transdermal delivery, such hydrogel patches have also found applications in cardiac therapy, cancer research, and biosensing, among other applications. In this mini-review, we critically discuss the challenges of fabricating multifunctional adhesive hydrogel patches. Furthermore, we introduce some of the chemical strategies involved with fabricating the patches. We also review their emerging biomedical applications. Finally, we explore their potential future in the flourishing field of tissue engineering and drug delivery